Morphologic, histochemical and vascular perfusion studies of methylcholanthrene-induced fibrosarcomas demonstrated that the growth characteristics and metastatic capabilities of each tumor line varied with their site of implantation into syngeneic rats. With subcutaneous injections, 10 to the 5th power cells were required to achieve uniform tumor takes due to marginal survival of the inoculum in these relatively avascular sites. After neovascularization, the sarcomas grew as encapsulated, locally invasive tumors which did not metastasize. Injections with 10 to the 2nd power sarcoma cells beneath the renal capsule yielded 100% tumor takes with increases in weight and cellularity at rates 3-5 times greater than seen in subcutaneous tumors. The renal sarcomas rapidly infiltrated the cortex; invaded renal veins and produced pulmonary metastases in 90% of the hosts within 2-3 weeks. At both sites, the enlarging sarcomas developed numerous microinfarcts due to thrombosis and invasion of the tumor vasculature. These sarcomas were heavily infiltrated with macrophages which tended to sequesten in zones of cellular injury without influencing tumor growth or metastasis. When injected intravenously, cells from the renal and subcutaneous sarcomas were equally capable of producing pulmonary metastases. Identical infusions into the portal vein yielded only hepatic metastases, while injection of the sarcoma cells into the splenic and superior mesenteric arteries failed to induce tumor growth at any site. These results cannot be explained by the Fidler hypothesis and suggest that metastases with this tumor model result from cellular aggregates which lodge in the first capillary bed encountered where their subsequent growth is determined by the local microenvironment.